缺血后处理减轻离体肥大大鼠心脏的缺血/再灌注损伤

[Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart].

作者信息

Peng Long-yun, Ma Hong, He Jian-gui, Gao Xiu-ren, Zhang Yan, He Xiao-hong, Zhai Yuan-sheng, Zhang Xue-jiao

机构信息

Cardiovascular Research Institute of Sun Yat-sen University, Department of Cardiovascular Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2006 Aug;34(8):685-9.

PMID:17081389

Abstract

OBJECTIVE

To explore the effects of ischemic postconditioning on ischemia/reperfusion injury in isolated hypertrophied rat heart and investigate the signal transduction pathway changes induced by ischemia postconditioning.

METHODS

Cardiac hypertrophy was induced in rats by abdominal aortic banding, and isolated hypertrophied rat heart ischemia/reperfusion model was made by Langendorff technique to evaluate the effects of ischemia postconditioning on left ventricular systole pressure, coronary artery flow, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) release, myocardial infarction size, and the level of myocardial phospho-protein kinase B/Akt (Ser473), phospho-glycogen synthase kinase-3beta (Ser9). Following groups were studied (n = 12 each group): IR, 30 min ischemia (I)/60 min Reperfusion (R); Post: 30 min ischemia, 6 circles of 10 s I/10 s R followed by 60 min R; Post Wort: 30 min ischemia, 6 circles of 10 s I/10 s R, wortmannin (10(-7) mol/L) followed by 60 min R; Wort: 30 min ischemia, wortmannin (10(-7) mol/L) followed by 60 min R.

RESULTS

Left ventricular systolic pressure and coronary artery flow were significantly increased, myocardial infarction size and the release of CPK, LDH significantly reduced in Post group compared to that in IR group. Phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) levels were also significantly higher in Post group than that in IR group. Phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin prevented the increase of phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) induced by ischemic postconditioning, but only partly abolished the cardioprotection of ischemic postconditioning.

CONCLUSION

Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart. The cardioprotective effects of ischemic postconditioning were partly mediated through PI3K/Akt/GSK-3beta signaling pathway.

摘要

目的

探讨缺血后处理对离体肥大大鼠心脏缺血/再灌注损伤的影响，并研究缺血后处理诱导的信号转导通路变化。

方法

采用腹主动脉缩窄法诱导大鼠心脏肥大，运用Langendorff技术制备离体肥大大鼠心脏缺血/再灌注模型，以评估缺血后处理对左心室收缩压、冠状动脉血流量、肌酸磷酸激酶（CPK）和乳酸脱氢酶（LDH）释放、心肌梗死面积以及心肌磷酸化蛋白激酶B/Akt（Ser473）、磷酸化糖原合成酶激酶-3β（Ser9）水平的影响。研究以下几组（每组n = 12）：IR组，30分钟缺血（I）/60分钟再灌注（R）；后处理组：30分钟缺血，10秒缺血/10秒再灌注共6个循环，随后60分钟再灌注；后处理+渥曼青霉素组：30分钟缺血，10秒缺血/10秒再灌注共6个循环，加入渥曼青霉素（10⁻⁷mol/L），随后60分钟再灌注；渥曼青霉素组：30分钟缺血，加入渥曼青霉素（10⁻⁷mol/L），随后60分钟再灌注。

结果

与IR组相比，后处理组左心室收缩压和冠状动脉血流量显著增加，心肌梗死面积以及CPK、LDH释放显著减少。后处理组磷酸化蛋白激酶B/Akt（Ser473）和磷酸化糖原合成酶激酶-3β（Ser9）水平也显著高于IR组。磷脂酰肌醇3激酶（PI3K）抑制剂渥曼青霉素可阻止缺血后处理诱导的磷酸化蛋白激酶B/Akt（Ser473）和磷酸化糖原合成酶激酶-3β（Ser9）增加，但仅部分消除缺血后处理的心脏保护作用。